This invention relates to a novel lyophilization method for particles, e.g., latex particles, which may be reagent-coated, such that the lyophilized product reconstitutes to an unagglutinated suspension, and remains stable and active while stored at about 4.degree. C. More particularly, this invention relates to a lyophilization procedure which employs the use of a cryoprotective agent which provides an inert amorphous network formed of macromolecular material which encapsulates the particles in spaced fashion and minimizes the "volume excluding effect" and, in addition, may include a zwitterionic buffer which neutralizes reactive but unprotected sites on the particles.
Often, reagents are coupled to reactive sites on the surface of particles, which may not be completely neutralized or blocked by the coupling reaction. It is evident that any residual reactive sites may eventually cause undesirable non-specific agglutination between the particles by bridging reactions.
In the past, the reconstitution of lyophilized reagent-coated particles, e.g., latex employed in particle-agglutinating immunoassays, had the severe disadvantage in that sonication of the reconstituted suspension was required to break up non-specifically agglutinated particles resulting from the effects of freeze-drying or lyophilization.
With the method of the present invention, it is possible to lyophilize particles, which may be reagent-coated, to preserve the activity of reagent and avoid spurious and non-specific agglutination of the particles to maintain the original state of agglutination of the suspension upon reconstitution. For example, if a monodisperse latex is lyophilized by the method of the invention, a substantially monodispersed latex suspension is obtained upon reconstitution.